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Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT00517907
Other study ID # PIF1BMT-HMO-CTIL
Secondary ID
Status Not yet recruiting
Phase Phase 1
First received August 16, 2007
Last updated June 10, 2015
Start date January 2016
Est. completion date January 2018

Study information

Verified date August 2008
Source Hadassah Medical Organization
Contact Reuven Or, MD
Phone +972-2-677-8357
Email reuvenor@hadassah.org.il
Is FDA regulated No
Health authority Israel: Israeli Health Ministry Pharmaceutical Administration
Study type Interventional

Clinical Trial Summary

The primary goal of this study is to determine the safety and tolerability of a novel peptide - preimplantation factor (PIF-1) - in patients who develop acute steroid-resistant graft-versus-host disease (GVHD) after matched bone marrow transplant (BMT).

Following matched BMT, patients will be placed on standard GVHD preventive therapy (cyclosporine); those who do not respond to cyclosporine are placed on a high-dose steroid regimen for 3 days. Patients that do not respond to this standard treatment will be given PIF-1 subcutaneously for 14 days.

Clinical data and samples will be collected, during PIF-1 administration and for an additional three months thereafter, to examine the long-term effect of PIF-1 treatment on the patients' GVHD status.


Description:

Allogeneic BMT is a well-established treatment modality for malignant and non-malignant hematological diseases. Mature donor T cells within the stem-cell graft are the main mediators of the beneficial immune effects, but they are also responsible for the induction of GVHD, which becomes the major cause of morbidity and mortality post-transplant. Acute GVHD occurs within a 100-day period post-transplant and generally is manifested by dermatitis, enteritis, and hepatitis. The treatment of GVHD continues to be a challenge. To eliminate undesirable host-derived hematopoietic elements before BMT, patients are traditionally treated with myeloablative conditioning regimens involving high-dose chemotherapy and total-body irradiation. Standard GVHD prophylaxis and therapy comprise drugs that cause generalized immune suppression and place patients in danger of opportunistic infections and tumor relapse. For acute GVHD prevention, cyclosporine is often used; however, it is frequently necessary to administer long-term high-dose steroids as well.

An acute GVHD patient's lack of response to steroids is associated with poor prognosis. The ideal prophylaxis treatment for BMT patients would be one that prevented the graft from attacking the host, and that modulated the host's immune response so that it would accept the transplant, while maintaining its ability to protect the body against opportunistic hostile agents.

Pregnancy is an immune paradox: it allows maternal (host) acceptance of a semi-allograft (embryo), while it does not cause graft-versus-host or host-versus-graft reactions against the host/mother, or immune suppression. Therefore, the pregnant immunological status is compatible with the desired immune profile in patients undergoing BMT. By replicating the immune profile present in pregnancy in BMT patients, we may be able to reduce the occurrence of GVHD-related morbidity and mortality rates.

Preimplantation factor (PIF-1) is a novel, embryo-secreted peptide whose synthetic version matches the native peptide's properties. PIF-1 appears to play an important role in mediating the maternal response to pregnancy in mammals. In preclinical studies, PIF-1 has been found to be effective in preclinical BMT-GVHD models, without apparent toxicity.


Recruitment information / eligibility

Status Not yet recruiting
Enrollment 6
Est. completion date January 2018
Est. primary completion date January 2018
Accepts healthy volunteers No
Gender Both
Age group 14 Years to 70 Years
Eligibility Inclusion Criteria:

- Acute steroid-resistant GVHD post matched BMT

Exclusion Criteria:

- Morbidity unrelated to GVHD

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment


Related Conditions & MeSH terms


Intervention

Drug:
Preimplantation factor (PIF-1)
The study will include 6 patients and will last for at least six months. The first three patients will receive PIF-1 (0.5 mg/kg/day for 14 days) by subcutaneous injection. The dosage in the next three patients may be increased to 1 mg/kg/day for 14 days. Patients will be treated serially: each patient will be followed for 2 weeks after cessation of PIF-1 administration before the next patient begins PIF-1 administration.

Locations

Country Name City State
Israel Hadassah Medical Organization Jerusalem

Sponsors (2)

Lead Sponsor Collaborator
Hadassah Medical Organization BioIncept LLC

Country where clinical trial is conducted

Israel, 

Outcome

Type Measure Description Time frame Safety issue
Primary Safety and tolerability of PIF-1 in steroid-resistant patients who develop acute GVHD, as evidenced by clinical and laboratory indices within 90 days after first PIF-1 injection Yes
Secondary Therapeutic effect of PIF-1 on participants' acute GVHD status, as determined by comparison with the clinical and laboratory indices before intervention within 90 days after first PIF-1 injection No
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